TP53 copy number expansion correlates with the evolution of increased body size and an enhanced DNA damage response in elephants

A major constraint on the evolution of large body sizes in animals is an increased risk of developing cancer. There is no correlation, however, between body size and cancer risk. This lack of correlation is often referred to as Petos Paradox. Here we show that the elephant genome encodes 20 copies of the tumor suppressor gene TP53 and that the increase in TP53 copy number occurred coincident with the evolution of large body sizes, the evolution of extreme sensitivity to genotoxic stress, and a hyperactive TP53 signaling pathway in the elephant (Proboscidean) lineage. Furthermore we show that several of the TP53 retrogenes (TP53RTGs) are transcribed and likely translated. While TP53RTGs do no